Fast-acting Insulins from Cone Snails

Model showing how mini-insulin (mini-Ins, gold and green) binds human insulin receptor (hIR, powder blue, magenta and tan) and replaces key interactions made by the terminal segment of human insulin (h-Ins, black).

Faster acting human insulins are needed to improve the efficacy of diabetic insulin pumps. Over the past few years, collaborating teams led by Olivera, Safavi-Hemami, Schlegel, Yandell, and Chou have made the remarkable discovery that fish-hunting cone snails use fast-acting insulins to inactivate their prey by inducing hypoglycemia. The team characterized these toxins and used the information gained to design a new fast-acting, stable human mini-insulin analog that has more rapid onset than current competitors in porcine diabetes models.

References:

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Specialized insulin is used for chemical warfare by fish-hunting cone snails. Safavi-Hemami H, Gajewiak J, Karanth S, Robinson SD, Ueberheide B, Douglass AD, Schlegel A, Imperial JS, Watkins M, Bandyopadhyay PK, Yandell M, Li Q, Purcell AW, Norton RS, Ellgaard L, Olivera BM. Proceedings of the National Academy of Sciences USA. 2015 Feb;112(6):1743.

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Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor. Ahorukomeye P, Disotuar MM, Gajewiak J, Karanth S, Watkins M, Robinson SD, Flórez Salcedo P, Smith NA, Smith BJ, Schlegel A, Forbes BE, Olivera B, Hung-Chieh Chou D, Safavi-Hemami H. Elife. 2019 Feb;8. pii:e41574.

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